Process for effecting sterile connections of medical tubing by way of terminally sterilizing an isolated fluid filled connected area

ABSTRACT

A process and apparatus for effecting sterile connections of medical tubing by way of terminally sterilizing an isolated fluid filled connected area with the steps of: isolating the terminal ends of two sealed tubing leads, removing the sealed terminal ends of each tube by cutting off these ends and discarding same, joining the resulting open ends of the respective tube leads together so as to provide a hermetic seal, further isolating a portion of fluid present in one or both of the tube leads, introducing this isolated fluid into the non)-sterile zone created by the opening of the tube ends, exposing the remaining isolated area to sufficient light radiation to sterilize all fluid and surfaces inside the connection area and removing the remaining isolation devices to open a sterile fluid pathway and a system/apparatus for effecting such sterile connections comprising the selection of tubing materials with high ultraviolet light transmission coefficient and with diameter and wall thickness suitable for both light transmission and functional integrity and which may be joined together via heat sealing or mechanical methods, making use of the presence of light transmissive sterile fluid in one or both of the lines (tubes) to be connected by isolating a quantity of this fluid to be transferred to the sterilization zone, and transferring this fluid to the connection zone to be sterilized.

BACKGROUND OF THE INVENTION

Medical products manufacturers and clinicians, including bloodcollection and storage operators, have frequent need to make a fluidtransfer between two or more sterile containers or systems by way oftubing connecting these containers. In the manufacturing environment, itis often necessary to sterilize components or subassemblies of a drug ordevice by different methods. For example, in a complex productincorporating both a fluid container and a dry set assembly, thesolution container may be steam sterilized whereas the set or othercomponents would not be compatible with steam processing. In such acase, the dry components may be terminally sterilized with gas orradiation. The problem arising herewith is how to join these componentstogether as an integrated sterile product when the sterility of thecomponents is compromised in the process of making the connection. Inthe typical clinical setting, contents from a blood collection containerneed to be transferred to other sterile containers. Again, the processof making the connection may compromise the sterility of both systems tobe connected.

Technologies are currently available and in use in the marketplace toaddress this need. These technologies may be grouped into threedifferent approaches to the problem of sterility. The first group seeksto maintain the sterility of the connected area through passive meansincluding contamination control measures. A second endeavors to create asterilizing field or plasma in which the connection is effected. A thirdapproach performs a terminal sterilization on the affected area afterthe connection is completed. The present invention utilizes thisterminal sterilization approach which is considered very reliable withrespect to sterility assurance.

Prominent among current technologies is a patented process thatincorporates a high voltage (>300 Kev) electron beam to sterilize theconnection. In this process (U.S. Pat. No. 5,009,654 and 5,496,302)tubing leading from components sterilized individually by separatemethods is clamped near their terminal ends to maintain sterileintegrity during the connection process. Each terminal end is cut off,removed, and the ends are then connected together by heat-sealing,solvent bonding, or other methods. Radiation is then applied to the areabetween the clamps to terminally sterilize and then clamps are removed,opening a sterile pathway. The present invention incorporates someaspects of the above process with additional steps and elements, whichserve to create a significant improvement.

The prior technology to which the present invention is most relevant isdeficient in its economy. The cost to implement and operate a highvoltage electron beam system is high. Special facilities expense isnecessary to provide shielding from x-rays and to assure that thepossibility for human exposure is minimized. Customized materialshandling equipment is required to transport product through the electronbeam system. The factory floor space required exceeds that of thepresent invention.

The present invention addresses these deficiencies in that certainalternate energy sources such as pulsed UV light sterilizing systemsoperate at faster rates, within a smaller floor space, and at less costthan high voltage electron beams. The system also operates withoutcreating ionizing radiation or other potential work environment hazards.In order to gain these benefits, a new assembly process comprising thesteps described in this application is necessary.

FIELD OF THE INVENTION

This invention relates generally to the field of medical drug and devicemanufacturing, to the field of clinical medical device operations, andmore particularly to a process for effecting sterile connections ofmedical tubing by way of terminally sterilizing an isolated fluid filledconnected area.

OBJECT OF THE INVENTION

The primary object of the invention is to provide a sterile connectionby terminally treating an isolated connected area after it is resealed.

Another object of the invention is to enable light energy to be employedfor terminally sterilizing tubing connections.

Another object of the invention is to provide a more cost effectivealternative to methods employing ionizing radiation.

A further object of the invention is to permit implementation of sterileconnection technology with less facilities and installation investmentthan ionizing radiation alternatives.

Yet another object of the invention is to reduce factory floor spacerequirements from that required by ionizing radiation alternatives.

Still yet another object of the invention is to enable higher levels ofmicrobial inactivation than that provided by other non-ionizingradiation alternative methods such as continuous wave ultravioletradiation.

Another object of the invention is to take opportune advantage of fluidspresent in the tubing to be connected.

Another object of the invention is to permit use of a range of olefinpolymers for the tubing material.

Other objects and advantages of the present invention will becomeapparent from the following descriptions, taken in connection with theaccompanying drawings, wherein, by way of illustration and example, anembodiment of the present invention is disclosed.

SUMMARY OF THE INVENTION

In accordance with a preferred embodiment of the invention, there isshown a process for effecting sterile connections of medical tubing byway of terminally sterilizing an isolated fluid filled connected areahaving the steps of isolating the terminal ends of two tubing leads tocompletely close the respective leads to the passage of contaminants;removing the sealed terminal ends of each tube; joining the resultingopen ends of the respective tube leads together so as to provide ahermetic seal and creating a non-sterile zone; further isolating aportion of fluid present in one or both of the tube leads adjacent tosaid zone; introducing said isolated fluid into said non-sterile zone;exposing the non-sterile zone to means for sterilizing all fluid andsurfaces inside said zone; and removing any remaining isolation means toopen a sterile fluid pathway.

In accordance with another preferred embodiment, there is shown anapparatus for effecting sterile connections for the flow of biologicalfluids having two sections of tubing having a high ultraviolet lighttransmission coefficient, wherein said tubing is joinable andselectively isolatable in sections for exposure of selected sections tosterilization means to create a sterile fluid path in joined tubing.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1. Cross Sectional View of Clamped Sterile Tubes Prior toConnection Representing the First Process Step.

FIG. 2. Cross Sectional View of Tubes Prior to Joining Representing theSecond Process Step.

FIG. 3. Cross Sectional View of Joined Tubing Representing the ThirdProcess Step.

FIG. 4. Cross Sectional View of Isolated Diluent in the TubingRepresenting the Fourth Process Step.

FIG. 5. Cross Sectional View of Non-sterile Zone of Connected TubingPrior to Sterilization Representing the Fifth Process Step.

FIG. 6. Cross Sectional View of Non-sterile Zone IllustratingSterilization Treatment Area Representing the Sixth Process Step.

FIG. 7. Cross Sectional View of Open Sterile Pathway IllustratingCompleted Sterile Connection and Representing the Final Process Step.

FIG. 8. Illustration of Alternate Embodiments of Joining Methods.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Detailed descriptions of the preferred embodiment are provided herein.It is to be understood, however, that the present invention may beembodied in various forms. Therefore, specific details disclosed hereinare not to be interpreted as limiting, but rather as a basis for theclaims and as a representative basis for teaching one skilled in the artto employ the present invention in virtually any appropriately detailedsystem, structure or manner.

In the particular method illustrated in FIGS. 1-8, certain stepsconstitute current practice, represent prior art, and serve as a commonstarting point for the preferred embodiment. These steps relate to theclamping, cutting, and joining of medical tubing segments. Additionally,the practice of terminally sterilizing the isolated segments of tubingjoined in such a manner with a high-voltage electron beam system alsoconstitutes prior art and is currently employed in the industry.

Pursuant to the present invention, provision is made for selection oftubing materials with high coefficient of UV transmission, havingdiameter and wall thickness to properly function, and for introductionof diluent fluid into the sterilization zone so that alternative energysources such as pulsed broad spectrum light including particularly theultraviolet wavelengths may be employed in effecting sterileconnections. This light energy is transmitted through the tubing anddiluent fluid sterilizing both in a short flash of high intensity.

The sterilization described above is made possible through isolating avolume of clear fluid, either already present in the wet leg of the tubeleads to be connected or introduced into one or both of the leads to beconnected. Disposable clamps or other mechanical devices, whicheffectively close off the tubing not permitting the passage of fluids,air, or potential microbial contamination, may provide this isolation.After such isolation is made then the clamp, or other device initiallyapplied to the wet leg tube lead, is released or removed permitting thefluid formerly isolated in this leg to flow into the larger segment ofconnected tubing defined by the location of the Clamps in FIGS. 4, 5,and 6.

The purpose for this introduction of fluid into the kill zone is toenhance the capacity of certain high intensity pulsed light technologyto inactivate microbial spore populations traditionally used to measurethe effectiveness of terminal sterilization processes. Challengeorganisms in such a diluent suspension may be more vulnerable toinactivation (kill) than challenge organisms inoculated by the dropmethod upon a dry tubing surface. This assertion has been demonstratedthrough numerous experiments employing high intensity pulsed light tokill bacterial spores on both dry surfaces and in solution containers(filled bottles). An industry accepted method for inoculating a drysurface to be sterilized is to place a drop of liquid containingapproximately 1 million (1×10⁶) organisms per milliliter on the surfaceto be treated and allowing this droplet to thoroughly dry. During thisdehydrating process, some of the bacterial spores tend to layer uponeach other. During the subsequent sterilization, spores on the surfacelayer absorb more energy than those located under the surface or atlower layers, the topmost spores in effect shadowing others. The resultmay be incomplete kill of all the organisms present. Studies have showna reduction of two to six logs of the spore challenge typically may beachieved with high intensity pulsed light systems. The standard methodfor measuring the sterilizing effects of a process on a filled containerdiffers slightly in that the challenge inoculum is injected into thefluid to be sterilized. It is assumed that the internal containersurfaces and the contained solution will be sterilized. When mostbacterial spores utilized for sterility validations are injected into aliquid, the spores tend to be more evenly dispersed within thesuspension than those in a dried droplet. Typical challenge levels are1×10⁶ to 1×10⁸ organisms per milliliter of fluid. When exposed to thesame sterilizing energy as samples having been drop inoculated, fluidcontainers typically may yield levels of kill of 6 to 8 logs. It is heldthat this improved result over drop inoculation is due primarily to thegreater degree of dispersion of the challenge bacterial spores in/on thesurfaces to be treated. Therefore, the present invention introducesfluid into the segment of tubing to be sterilized for two reasons.First, this segment becomes essentially a fluid container and may thenbe challenged according to proven and accepted methods for fluidcontainers. Secondly, if a drop challenge were to be applied to innertube surfaces to be sterilized, the introduction of fluid to thissegment would serve to dilute and further disperse the challengematerial so as to reduce and minimize the layering as earlier described.

Additionally, the connection of the tubing to be joined must beperformed in such a way as to facilitate light transmission to allinterior tubing surfaces. As the light energy must first penetrate thetube wall before it can act upon biological material in the interiorspaces, it becomes important to avoid creating areas of high tubingcross sectional thickness, which would absorb the energy. In the presentinvention, the joining methods employed minimize this “shadowing”effect.

In operation, the essential steps comprising the process will be asfollows: Turning first to FIG. 1, the tubes leading from the sterilesystems to be joined are clamped with medical grade plastic slide clamps(12, 13) or facsimile at a point approximately 1 or more inches from thesealed terminal ends (16, 17) of the respective tubes (14, 15). Turningto FIG. 2., the tube ends from both leads are cut away and discardedleaving open sections of tubing (14, 15). Next, in FIG. 3., tube endsare joined together by way of heat sealing (104) or other means creatinga non-sterile connection zone (105). In FIG. 4. It is illustrated that athird clamp of the type used in the FIG. 1 is applied to the “wet” lineat a point upstream of the original clamp on this line (158). Thedistance from the third clamp (158) to the original clamp on the line(12) may be varied to control the quantity of diluent (150) introducedinto segment to be sterilized (205). The original clamp on the “wet”line (12) is then removed or otherwise released. Referring to FIG. 5.,the prior step permits fluid from the segment isolated by the thirdclamp (150) to flow into the non-sterile segment (205). Mechanicalassistance may be applied in transferring this fluid into thenon-sterile segment. Finally, the segment or area then isolated by theremaining two clamps (205) is sterilized by means of non-ionizingradiation applied from outside the tube. As illustrated in FIG. 6.,pulsed broad-spectrum light will penetrate the tube walls (259) andsolution isolated by the clamps (158, 13) inactivating a minimum of 6logs of microbial challenge in the region defined by the treatment zone(257). Referring to FIG. 7., the clamps (158, 13 from FIG. 6.) areremoved or otherwise opened creating a sterile path for the fluids (301)to be transferred between systems.

Alternate methods of connecting the tubing may include those depicted inFIG. 8 wherein a light transmissive plastic sleeve (351) is sealed byheat or other means to the tube ends (14, 15) or a mechanical connector(357) may also be employed provided UV light transmission and functionalrequirements are satisfied.

The advantages of this process include the speed with whichsterilization may be effected versus existing electron beam systems andthe reduced cost of implementing a pulsed light sterilization systemversus a high voltage electron beam system.

High intensity pulsed light sterilization systems employ advancedelectrical capacitor and switching technology to generate and deliververy short, high voltage bursts of electricity to an inert gas filledtube housed within a flash assembly. This flash is directed toward theproduct to be treated with light waves of various spectra penetratinglight transmissive materials in the product. Bacteria absorbing thisenergy are inactivated. The present invention makes no claim to thetechnology of pulsed light sterilization per se.

While the invention has been described in connection with a preferredembodiment, it is not intended to limit the scope of the invention tothe particular form set forth, but on the contrary, it is intended tocover such alternatives, modifications, and equivalents as may beincluded within the spirit and scope of the invention as defined by theappended claims.

What is claimed is:
 1. A process for effecting sterile connections ofmedical tubing by way of terminally sterilizing an isolated fluid filledconnected area comprising the steps of: a. Isolating the terminal endsof two tubing leads to completely close the respective leads; b.Removing the sealed terminal ends of each tube; C. Joining the resultingopen ends of the respective tube leads together so as to provide ahermetic seal and creating a non-sterile zone; d. Further isolating aportion of fluid present in one or both of the tube leads adjacent tosaid zone; e. Introducing said isolated fluid into said non-sterilezone; f. Exposing the non-sterile zone to means for sterilizing allfluid and surfaces inside said zone; and g. Removing any remainingisolation means to open a sterile fluid pathway.
 2. A process as claimedin claim 1 wherein said isolation is by pinching the tubing.
 3. Aprocess as claimed in claim 1 wherein said isolation is by clamping thetubing.
 4. A process as claimed in claim 1 wherein said tubing leads aresealed at their ends.
 5. A process as claimed in claim 1 wherein saidjoining is by heatseal butt-welding.
 6. A process as claimed in claim 1wherein said joining is by a connector.
 7. A process as claimed in claim6 wherein said connector is a barbed-ended tube.
 8. A process as claimedin claim 6 wherein said connector is a generally cylindrical sleeve. 9.A process as claimed in claim 1 wherein said sterilization is by highintensity pulsed light radiation.
 10. A process as claimed in claim 1further comprising the step of contacting substantially all surfaces ofthe non-sterile zone with the sterilized fluid.
 11. A process as claimedin claim 1 wherein said contaminants may be liquid, air, or microbial.12. An apparatus for effecting sterile connections for the flow of drugand biological fluids comprising: Two sections of tubing having a highultraviolet light transmission coefficient, wherein said tubing isjoinable and selectively isolatable in sections for exposure of selectedsections to sterilization means to create a sterile fluid path in joinedtubing.
 13. An apparatus as claimed in claim 12 wherein said isolationis by pinching the tubing.
 14. An apparatus as claimed in claim 12wherein said isolation is by clamping the tubing.
 15. An apparatus asclaimed in claim 12 wherein said joining is by heat seal welding.
 16. Anapparatus as claimed in claim 12 wherein said sterilization means is byhigh intensity pulsed light radiation.